The genetic basis of tumorigenic responses to endogenous or inoculated C-type viruses is being studied in a variety of strain crosses. The major determinants of spontaneous leukemias in hybrids with AKR have been shown to be the endogenous ecotropic virus inducing loci, the Fv-1 gene, and the Rmcf gene. In mice inoculated with MCF 247 virus, inheritance of an ecotropic virus-inducing locus of major importance for leukemogenicity. The Rmcf gene, which specifically inhibits infectivity of MCF viruses, is a strong determinant of leukemogenicity by MCF 247 and Friend helper virus and is possibly a minor determinant of ecotropic Moloney and Gross virus leukemogenicity. The effect of this gene on a variety of retroviral diseases is under study, including spontaneous B-cell lymphomas in high virus congenic mice, mice inoculated with erythroblastic or myeloid leukemia-inducing viruses, and mice inoculated with a neuroparalytic retrovirus.